Eric T. Payne

Seizure burden is independently associated with short term outcome in critically ill children

Seizures are common among critically ill children, but their relationship to outcome remains unclear. We sought to quantify the relationship between electrographic seizure burden and short-term neurological outcome, while controlling for diagnosis and illness severity. Furthermore, we sought to determine whether there is a seizure burden threshold above which there is an increased probability of neurological decline. We prospectively evaluated all infants and children admitted to our paediatric and cardiac intensive care units who underwent clinically ordered continuous video-electroencephalography monitoring over a 3-year period. Seizure burden was quantified by calculating the maximum percentage of any hour that was occupied by electrographic seizures. Outcome measures included neurological decline, defined as a worsening Paediatric Cerebral Performance Category score between hospital admission and discharge, and in-hospital mortality. Two hundred and fifty-nine subjects were evaluated (51% male) with a median age of 2.2 years (interquartile range: 0.3 days-9.7 years). The median duration of continuous video-electroencephalography monitoring was 37 h (interquartile range: 21-56 h). Seizures occurred in 93 subjects (36%, 95% confidence interval = 30-42%), with 23 (9%, 95% confidence interval = 5-12%) experiencing status epilepticus. Neurological decline was observed in 174 subjects (67%), who had a mean maximum seizure burden of 15.7% per hour, compared to 1.8% per hour for those without neurological decline (P < 0.0001). Above a maximum seizure burden threshold of 20% per hour (12 min), both the probability and magnitude of neurological decline rose sharply (P < 0.0001) across all diagnostic categories. On multivariable analysis adjusting for diagnosis and illness severity, the odds of neurological decline increased by 1.13 (95% confidence interval = 1.05-1.21, P = 0.0016) for every 1% increase in maximum hourly seizure burden. Seizure burden was not associated with mortality (odds ratio: 1.003, 95% confidence interval: 0.99-1.02, P = 0.613). We conclude that in this cohort of critically ill children, increasing seizure burden was independently associated with a greater probability and magnitude of neurological decline. Our observation that a seizure burden of more than 12 min in a given hour was strongly associated with neurological decline suggests that early antiepileptic drug management is warranted in this population, and identifies this seizure burden threshold as a potential therapeutic target. These findings support the hypothesis that electrographic seizures independently contribute to brain injury and worsen outcome. Our results motivate and inform the design of future studies to determine whether more aggressive seizure treatment can improve outcome.

Electrographic seizures in pediatric ICU patients Cohort study of risk factors and mortality

Objectives: We aimed to determine the incidence of electrographic seizures in children in the pediatric intensive care unit who underwent EEG monitoring, risk factors for electrographic seizures, and whether electrographic seizures were associated with increased odds of mortality. Methods: Eleven sites in North America retrospectively reviewed a total of 550 consecutive children in pediatric intensive care units who underwent EEG monitoring. We collected data on demographics, diagnoses, clinical seizures, mental status at EEG onset, EEG background, interictal epileptiform discharges, electrographic seizures, intensive care unit length of stay, and in-hospital mortality. Results: Electrographic seizures occurred in 162 of 550 subjects (30%), of which 61 subjects (38%) had electrographic status epilepticus. Electrographic seizures were exclusively subclinical in 59 of 162 subjects (36%). A multivariable logistic regression model showed that independent risk factors for electrographic seizures included younger age, clinical seizures prior to EEG monitoring, an abnormal initial EEG background, interictal epileptiform discharges, and a diagnosis of epilepsy. Subjects with electrographic status epilepticus had greater odds of in-hospital death, even after adjusting for EEG background and neurologic diagnosis category. Conclusions: Electrographic seizures are common among children in the pediatric intensive care unit, particularly those with specific risk factors. Electrographic status epilepticus occurs in more than one-third of children with electrographic seizures and is associated with higher in-hospital mortality.

Febrile infection‐related epilepsy syndrome treated with anakinra

Febrile infection‐related epilepsy syndrome (FIRES) is a devastating epileptic encephalopathy with limited treatment options and an unclear etiology. Anakinra is a recombinant version of the human interleukin‐1 receptor antagonist used to treat autoinflammatory disorders. This is the first report of anakinra for treatment of a child with super‐refractory status epilepticus secondary to FIRES. Anakinra was well tolerated and effective. Cerebral spinal fluid analysis revealed elevated levels of proinflammatory cytokines before treatment that normalized on anakinra, suggesting a potential pathogenic role for neuroinflammation in FIRES. Further studies are required to assess anakinra efficacy and dosing, and to further delineate disease etiology. Ann Neurol 2016;80:939–945

Electrographic seizures after convulsive status epilepticus in children and young adults: a retrospective multicenter study.

OBJECTIVE To describe the prevalence, characteristics, and predictors of electrographic seizures after convulsive status epilepticus (CSE). STUDY DESIGN This was a multicenter retrospective study in which we describe clinical and electroencephalographic (EEG) features of children (1 month to 21 years) with CSE who underwent continuous EEG monitoring. RESULTS Ninety-eight children (53 males) with CSE (median age of 5 years) underwent subsequent continuous EEG monitoring after CSE. Electrographic seizures (with or without clinical correlate) were identified in 32 subjects (33%). Eleven subjects (34.4%) had electrographic-only seizures, 17 subjects (53.1%) had electroclinical seizures, and 4 subjects (12.5%) had an unknown clinical correlate. Of the 32 subjects with electrographic seizures, 15 subjects (46.9%) had electrographic status epilepticus. Factors associated with the occurrence of electrographic seizures after CSE were a previous diagnosis of epilepsy (P = .029) and the presence of interictal epileptiform discharges (P < .0005). The median (p25-p75) duration of stay in the pediatric intensive care unit was longer for children with electrographic seizures than for children without electrographic seizures (9.5 [3-22.5] vs 2 [2-5] days, Wilcoxon test, Z = 3.916, P = .0001). Four children (4.1%) died before leaving the hospital, and we could not identify a relationship between death and the presence or absence of electrographic seizures. CONCLUSIONS After CSE, one-third of children who underwent EEG monitoring experienced electrographic seizures, and among these, one-third experienced entirely electrographic-only seizures. A previous diagnosis of epilepsy and the presence of interictal epileptiform discharges were risk factors for electrographic seizures.

Treatment Leading to Dramatic Recovery in Acute Hemorrhagic Leukoencephalitis

The clinical course, neuroimaging, neuropathological features, and management of a 7-year-old girl with acute hemorrhagic leukoencephalitis are reported. Treatment with subtotal bifrontal craniectomies for symptoms of imminent uncal herniation followed by high-dose corticosteroid therapy was associated with dramatic clinical recovery. This report highlights the utility of aggressive intervention in acute hemorrhagic leukoencephalitis, an otherwise fatal disorder.

Electroencephalography monitoring in critically ill children: Current practice and implications for future study design

Survey data indicate that continuous electroencephalography (EEG) (CEEG) monitoring is used with increasing frequency to identify electrographic seizures in critically ill children, but studies of current CEEG practice have not been conducted. We aimed to describe the clinical utilization of CEEG in critically ill children at tertiary care hospitals with a particular focus on variables essential for designing feasible prospective multicenter studies evaluating the impact of electrographic seizures on outcome.

Development and validation of a seizure prediction model in critically ill children

PURPOSE Electrographic seizures are common in encephalopathic critically ill children, but identification requires continuous EEG monitoring (CEEG). Development of a seizure prediction model would enable more efficient use of limited CEEG resources. We aimed to develop and validate a seizure prediction model for use among encephalopathic critically ill children. METHOD We developed a seizure prediction model using a retrospectively acquired multi-center database of children with acute encephalopathy without an epilepsy diagnosis, who underwent clinically indicated CEEG. We performed model validation using a separate prospectively acquired single center database. Predictor variables were chosen to be readily available to clinicians prior to the onset of CEEG and included: age, etiology category, clinical seizures prior to CEEG, initial EEG background category, and inter-ictal discharge category. RESULTS The model has fair to good discrimination ability and overall performance. At the optimal cut-off point in the validation dataset, the model has a sensitivity of 59% and a specificity of 81%. Varied cut-off points could be chosen to optimize sensitivity or specificity depending on available CEEG resources. CONCLUSION Despite inherent variability between centers, a model developed using multi-center CEEG data and few readily available variables could guide the use of limited CEEG resources when applied at a single center. Depending on CEEG resources, centers could choose lower cut-off points to maximize identification of all patients with seizures (but with more patients monitored) or higher cut-off points to reduce resource utilization by reducing monitoring of lower risk patients (but with failure to identify some patients with seizures).

Anesthetic-Related Neurotoxicity and Neuroimaging in Children: A Call for Conversation

Each year millions of young children undergo procedures requiring sedation or general anesthesia. An increasing proportion of the anesthetics used are provided to optimize diagnostic imaging studies such as magnetic resonance imaging. Concern regarding the neurotoxicity of sedatives and anesthetics has prompted the US Food and Drug Administration to change labeling of anesthetics and sedative agents warning against repeated or prolonged exposure in young children. This review aims to summarize the risk of anesthesia in children with an emphasis on anesthetic-related neurotoxicity, acknowledge the value of pediatric neuroimaging, and address this call for conversation.

Continuous electroencephalography for seizures and status epilepticus.

Purpose of review To discuss the use of continuous video-electroencephalographic (cEEG) monitoring among critically ill children at risk for electrographic seizures and status epilepticus. Recent findings Recent reports have demonstrated the growing, but heterogeneous, use of cEEG monitoring among North American pediatric institutions, and provided evidence for the high prevalence of subclinical seizures, particularly among encephalopathic patients with acute brain injury. Increasing seizure burden and status epilepticus have been shown to be independently associated with worse short-term and long-term outcomes. Summary Certain high-risk children frequently experience electrographic seizures and status epilepticus, often without clinical signs, necessitating the use of cEEG monitoring for their diagnosis and management. Although an increasing electrographic seizure burden and status epilepticus are independently associated with worse outcome, further studies are needed to determine whether aggressive use of antiepileptic drugs to reduce seizure burden can improve outcome.

Reply: The circular dilemma of seizure-induced brain injury

Sir, We thank Dr Grillo for his comments. A growing body of evidence from in vitro studies, animal models, observational studies in critically ill neonates, children and adults supports the hypothesis that electrographic seizures independently contribute to brain injury, whether they are clinically evident or not (Holmes, 2014). However, the relative contribution of seizures to brain injury clearly depends on the underlying aetiology (Hahn and Jette, 2013). In our recent study, the association between seizure burden and outcome …